Tumor-…

Researchers at Baylor College of Medicine and collaborating institutions have discovered new insights into tumor-induced B cell changes in blood and bone marrow of triple negative breast cancer patients. The findings, published in Nature Cell Biology, show two distinct patterns of B cell abnormalities that could serve as blood biomarkers for determining likelihood of response to standard-of-care chemotherapy and immunotherapy.

"Even with significant advances in immunotherapy, only about 15 to 20% of patients with triple negative breast cancer will benefit from this treatment," said corresponding author Dr. Xiang H.-F. Zhang, director of the Lester and Sue Smith Breast Center, McNair Scholar and professor of molecular and cellular biology at Baylor. "My lab is trying to understand why some cancers do not respond to treatment by examining the crosstalk between the tumor and the body. Many systemic changes arise because of how the body responds to the cancer."

A previous study from Zhang's lab showed that even before tumor metastasis, breast cancer remotely induces changes to immune cell development in the bone marrow. Building on those findings, Zhang's team examined changes in B cells from patient blood samples and identified three subgroups. The first group, TiBA-0, has no changes to B cells. The second group, TiBA-1, has a reduced number of B cells, likely due to competition with myeloid progenitors in the bone marrow microenvironment. The third group, TiBA-2, has an increased number of immature B cells, likely due to an excessive number of neutrophils preventing the B cells from maturing. In this group, immature B cells lead to an increase in exhausted T cells.

Researchers found that the B cell changes in both TiBA-1 and TiBA-2 types lead to an immunosuppressive effect and poorer response to treatment. In a study of 35 patients, 78.6% of TiBA-0 patients had a complete response to treatment with chemotherapy and immunotherapy, while only 33.3% of TiBA-1 and TiBA-2 patients had a complete response.

"These immune cell changes are not just happening locally inside the tumor. We see them systemically across the entire body, which means that we can identify these immune cell biomarkers with a simple blood draw," said Zhang, William T. Butler, M.D., Endowed Chair for Distinguished Faculty. He also is a member of the Dan L Duncan Comprehensive Cancer Center. "In the future, we may be able to stratify patients based on these biomarkers and determine which patients are less likely to respond to standard therapies and require additional treatment."

Zhang's team next will work with other researchers and clinicians at the Dan L Duncan Comprehensive Cancer Center to study the blood biomarkers in a larger patient group over multiple time points throughout treatment to learn more about how immune cells may change over time. His lab also is studying ways to reverse tumor-induced changes in bone marrow to restore normal production of immune cells.

Other contributors to this research include Xiaoxin Hao, Yichao Shen, Jun Liu, Angela Alexander, Ling Wu, Zhan Xu, Liqun Yu, Yang Gao, Fengshuo Liu, Hilda L. Chan, Che-Hsing Li, Yunfeng Ding, Weijie Zhang, David G. Edwards, Nan Chen, Azadeh Nasrazadani, Naoto T. Ueno and Bora Lim. The are affiliated with one or more of the following institutions: Baylor College of Medicine, Dan L Duncan Comprehensive Cancer Center, Chinese Academy of Medical Sciences and Peking Union Medical College, University of Texas MD Anderson Cancer Center, Zhejiang University and University of Hawai'i Cancer Center.

This research is supported by the U.S. Department of Defense, National Cancer Institute, Breast Cancer Research Foundation, McNair Medical Institute, National Institutes of Health and Cancer Prevention and Research Institute of Texas. See the publication for a full list of funding.